Friday, May 08, 2020

What are the arc (s?) of the normal aging heart ( the sedentary ageing heart and the exercising ageing heart).Are they different?

Humans seem good at finding patterns-sometimes even from patternless noise.One of the stories told by physiologists and cardiologists regarding the age related downhill course of cardiac function seems to go something like this.

One way to simplify cardiac function is to consider the two parts of the cardiac cycle,1) contraction and ejection of blood and 2) relaxation and the refilling of the ventricle.

There are data indicating that the first signs of an impending problem are seen in the filling phase ie. diastole.From extensive echocardiographic and invasive physiologic measurements in humans the following sequence can be sketched out and penciled in.

First, there is impaired relaxation following by decreased elastic recoil and later diminished compliance ( which is to say increased stiffness) and then -at least according to work from the IEEM group- remodeling of hearts with thicker walls and smaller ventricular volumes).Simply put- a sedentary ageing lifestyle leads to a small stiff heart and long time endurance exercise leads to a larger more easily filled heart.The contractile function of the heart is well preserved with ageing , at least as indicated by measurement of the resting ejection fraction.( increasing stroke volume with exercise is another matter as is left ventricular stress measured by speckle echo.)

This is largely consistent with the mainstream echocardiographic model which proposes a predictable,progressive process beginning with impaired relaxation,followed by decreased compliance and ultimately- as a compensation- elevated left side filling pressures.This model describes three phases of diastolic dysfunction indentifiable by combination of echo findings believed to reflect how well or poorly blood flows into the ventricles from the atrium. This model recognizes that the various indices ( e.g E/A ratio, IVRT,maximal E wave velocity and the time constant of isovolumic pressure decay (Tau) change with age so that what would be abnormal in a 20 year old is normal in a 75 year old.It is thought that that filling pressure can be estimated by use of this model. NOTE-see end note 1 for reference to data that challenges the mainstream model by in part providing data that cardiac cath measurements of left sided pressures do not regularly correspond with the three echo defined stages of diastolic dysfunction)

Next I consider what I have labelled as the "Dallas or IEEM theory" of cardiac ageing.

I do not know if Dr. Ben Levine would approve of my label or not. see end note 2

A series of articles from the University of Texas Southwestern Medical School and the IEEM have provided extensive invasive and noninvasive data regarding cardiac function at various ages and the effect of longtime endurance exercise versus sedentary ageing on cardiac structure and function.

Levine et al first demonstrated that lifelong endurance athletes ( 25 years or more of running a lot) had left ventricular compliance virtually identical to those of sedentary 20-30 years olds. Then they compared ventricular compliance in four groups of 25 each of people who exercised at various levels over a 25 years period. These were all subjects over the age of 64 and were screened to excluded pre-existing heart disease.Group 1 was sedentary people who exercised no more than one session per week. Group 2 were labelled "causal exercisers" and exercised 2-3 times per week. Group 3 (Labelled as committed exercisers}worked out 4-5 times per week and the "competitive" group trained 6-7 times per week and regularly raced.The racers had the most elastic or compliant ventricles while group 3 was "very close" in terms of ventricular compliance while groups 1 and 2 has significantly stiffer hearts.Note: while exercise seemed to help maintain compliance , long time endurance exercise did not mitigate the age related loss of ventricular relaxation-as measured by the isovolumic relaxation time (ivrt) which is the time from aortic valve closure to mitral value opening.

Next, Levine studied a group of 70 year old subjects and an vigorous exercise program was unsuccessful in improving the reduced compliance observed in that group. Next another study demonstrated that middle age subjects with a year long exercise program ( that involved in part high intensity interval training) were able to increase their ventricular compliance.This implies that past some point in time you cannot improve LV compliance with endurance training with some interval training but middle age may not be too late.This does definitely not mean that exercise for those 70 years of age and older gain no benefit from aerobic exercise,,just that it looks like they will not improve left ventricular compliance (at least withinthe time frame of Levine's subjects)

In another article Levine said that exercise in the range of that performed by the "committed exerciser" might be adequate.

My main question in this regard is "how much exercise "is sufficient to maintain a healthy compliant left ventricle." Levine's amazingly compliant (pun intended) subjects not only stuck with program for a full year but after the first 6 months participated in a hig intensity interval program using the demanding 4X4 workout program that involves 4 minutes of exercise at 95% of maximal heart rate followed by 4 minutes of rest done four times.

End note 1. Grant et al (Grant A, Grading diastolic function by echocardiography:hemodynamic validation of existing guidelines.Cardiovascular Ultrasound 2015 513 :28) compared echocardiography results with left heart catherization data in 460 patients.The data demonstrated that there were no differences in regard to left ventricular pressures between patients with normal diastolic function and those with grade 1 or 2 diastolic dysfunction but there were differences between normal and grade 3 diastolic dysfunction in patients with reduced ejection fraction.In those patients with preserved EF, there is no statistical difference between normal and any grade of diastolic dysfunction. (see figure 5 of their article which graphically illustrates the lack of the "predictable, progressive process "which characterizes the current paradigm.)If the detection of elevated LV pressures which generally correlates with exertional shortness of breath is in part the goal of echo studies of diastolic function it appears to not be reached based on Grant's data.

end note 2. Dr Ben Levine is the director of the Institute for Exercise and Enviromental Medicine (IEEM) housed at the Texas Health Presbyterian Hospital Dallas and professor at University of Medicine Southwestern. His group have done a series of comprehensive physiological studies on subjects recruited from the Dallas Heart Study, a population based sample of 6100 subjects in Dallas .

In a nut shell the concept is that everyone with aging develops some degree of diastolic dysfunction related to impaired relaxation and loss of diastolic suction,Later aging (particularly sedentary ageing) is associated with loss of ventricular compliance ( AKA increased stiffness). A long term endurance exercise program is capable of mitigating the changes in compliance but not the decrement in relaxation and diastolic suction. IEEM's studies further indicate that a sedentary lifestyle may lead to a small stiff heart which may be the precursor to heart failure with preserved ejection fraction (HFpEF) ) and the Dallas group suggest that an appropriate amount of endurance type exercise begun no later than early middle age may play an important role in the prevention of HFpEF.

"Humans are pattern-seeking story -telling animals and we are quite adept at telling stories about patterns, whether they exist or not".Michael Shermer.

End note 3:In 2008, Shermer coined the term "patternicity" -the tendency to find meaningful patterns in meaningless noise. I am not suggesting that the extensive,very carefully done research referenced above is meaningless noise.I just really like the quote but I certainty hope the "Dallas hypothesis" ( my term) is a reasonably accurate approximation of the ways things really are at least sometimes- having spent a lot of time running a lot over the last 40 plus years.

Saturday, April 25, 2020

The following is a quote from a commenter named Handle on Arnold Kling's blog from 4/25/20202 entitled Henderson-Wolfers Non-Debate.

"One of the most terrible things than can happen in our society is that some important and formerly neutral questions becomes politicized and the position one espouses become a strong signal of affiliation to a particular team....once there is a party line on the matter thinking ends all together."

Two examples-Several members of the Republican party appear in Congress not wearing masks
presumably to make a point. ER Nurses stage a counter protest against a open things up protest,shouting matches break out.

Thursday, April 16, 2020

The slipstream is the zone behind a person moving (walking, running,etc) which pulls the air along with the person.In the racing world it is known as drafting.

A recent news article about a study done by Belgian engineers has gone a bit viral itself.The wave of air flowing carrying respiratory droplets or drops in the wake of a runners goes behind him for distances greater than the magic 6 feet that we are admonished to respect as regards proximity to other humans in the world or preventive social distancing. At least the animations released by the researchers give that impression as do their data which at this writing has not yet been published in a peer reviewed journal.

If their animations reflect the actual path of exhaled particles,one might decide that even when you are out for a run to wear a mask at least some of the time.

See here for some questions and answers from one of the authors of the paper.

My personal take home is that when a runner passes me I should move to the side to avoid potential particles in his slipstream and ( with an abundance of caution) pull my mask up until the passer is 20 to 30 thirty feet away. In the increasingly unlikely instance in which I actually overtake a runner and pass her I should move to the side and keep to the side to keep the passed person out of my slipstream.

Perhaps the equivalent of "My mask protects you,your mask protects me" for runners could be
"I'll keep you out of my slipscreen,you keep me out of yours"

According to the authors data a cyclist should stay 60 feet directly behind the bike in front or keep off to the side. Also they suggest that 16 feet behind a walker and 32 feet behind a runner to be approximations of the "aerodynamically equivalent social distance" which is six feet for stationary people.

Sunday, March 29, 2020

Public face mask use appears to be common in Asian countries and also is now required in

the Czeck Republic where people wear masks as a civil duty with the shared realization that "I protect you by wearing a mask and you protect me by wearing a mask."

Corona virus is spread by droplets by infected persons even if they are asymptomatic and both simple surgical type face masks and the more expensive and protective N 95 masks can significantly reduce spread of coronavirus.

Both type of masks have been scarce in the US as Covid 19 cases exploded. Expectations and then realization of actual mask shortages in medical care facilities lead public health officials to discourage the public from using masks in the hope that more would be available for health care workers

Sometimes it has been argued that the masks were not effective when used by the public while at the same time saying that the masks should be reserved for medical personnel use in whose hands they would somehow offer important protection to them. Of course, protection is not a function of one's profession.

It is likely that it was believed that officially recommending masks would lead to a large public demand , making it even more difficult for health facilities to obtain masks.

As Covid 19 cases continue to increase and the mask shortage worsened, the CDC said that masks can be reused and ,that homemade masks and scarfs could be used as a last resort by health care workers. This was a major change in CDC recommendations.Home made masks and scarfs can be used to protect the public as well, although that was not said by CDC.

Jeremy Howard,a Deep Learning specialist from Stanford, has posted an excellent review of the use and value of face masks by the general public to decrease COVID spread and describes widespread use by the public in many countries.See here

He gives links to sites with important information on how to clean masks and how to make masks at home from towels, t shirts etc. Some may worry about being accused of taking masks away from doctors and nurses if they wear a mask in public. Home made masks hopefully defuse that issue.

Summary:
Covid 19 is spread by droplets by asymptomatic as well as symptomatic persons
Various kinds of masks decrease risk of spread
Masks can be made at home and worn in public without shame .A great DIY project
Masks protect others perhaps even more than they protect the wearer
It has been suggested that it would be unpatriotic for the public to wear masks.I suggest the opposite.
wearing masks is patriotic.An asymptomatic covid 19 infected person being in public exposing others to the disease is certainly not patriotic.
I am not recommending to bid up prices of masks,No one wants to take masks away from HCWs.
But if you already have masks on hand ,wear them .If not they really can be made at home and will offer some important protection . Yes, less than the properly fitted and correctly worn N 95 and less than surgical masks but significant protection nevertheless.
Bottom line wear masks in crowds (including grocery shoping)

Finally, imagine for a moment if only 25% of subway riders in New York (8 million riders per day) wore masks for the last 2 -3 weeks what the results might have been. Also imagine the potential benefit after we all come out emerge from sheltering in place how potentially important wide spread use of mask might be in decreasing the risk and/or impact of a second wave.

The following quote is from Scott Alexander writing on his blog slatestarcodex.com on 3/23/20 giving a detailed analysis on the research of various masks and the protection they provide;

". So should you wear a mask?

Please don’t buy up masks while there is a shortage and healthcare workers don’t have enough.

If the shortage ends, and wearing a mask is cost-free, I agree with the guidelines from China, Hong Kong, and Japan – consider wearing a mask in high-risk situations like subways or crowded buildings. Wearing masks will not make you invincible, and if you risk compensate even a little it might do more harm than good. Realistically you should be avoiding high-risk situations like subways and crowded buildings as much as you possibly can. But if you have to go in them, yes, most likely a mask will help.

In low-risk situations, like being at home or taking a walk, I mean sure, a mask might make you 0.0001% (or whatever) less likely to get infected. If that’s worth it to you, consider the possibility that you might be freaking out a little too much about this whole pandemic thing. If it’s still worth it, go for it.

You are unlikely to be able to figure out how to use an N95 respirator correctly. I’m not saying it’s impossible, if you try really hard, but assume you’re going to fail unless you have some reason to think otherwise. The most likely outcome is that you have an overpriced surgical mask that might make you incorrectly risk-compensate.

If you are a surgeon performing surgery, bad news. It turns out surgical masks are not very useful for you (1, 2)! You should avoid buying them, since doing so may deplete the number available for people who want to wear them on the subway."

"the massive impact of policies like those of Singapore or South Korea:

If people are massively tested, they can be identified even before they have symptoms. Quarantined, they can’t spread anything.

If people are trained to identify their symptoms earlier, they reduce the number of days in blue, and hence their overall contagiousness

If people are isolated as soon as they have symptoms, the contagions from the orange phase disappear.

If people are educated about personal distance, mask-wearing, washing hands or disinfecting spaces, they spread less virus throughout the entire period."

(note the blue and orange wording references refer to charts in his article)

Maybe it is this simple: If asymptomatic patients are not contagious, the masks only for the symptomatic rule works, but if the asymptomatic are contagious that rule does not work.

addendum: 4/11/20 Several glaring typos finally corrected.Also now the CDC has blessed the wearing of face masks by the general public, preferably of the home made variety.Two days ago at the grocery about 50% of the shoppers wore masks, most not of the DIY type.

Addendum 5/8/20 Today at Krogers only 2 of the approximately 40-50 person did not have masks.All of the store workers did and now they have erected plexiglass barriers shielding the checkers.

Wednesday, March 25, 2020

A recent article in the BMJ raised concern that drugs that inhibit parts of the RAAS system might be harmful to patients infected with the new novel corona virus known as SARS-COV2 while the disease it produces is named COVID 19.

Coarse grain epidemiologic data from the Wuhan outbreak indicated that one of the risk factors for bad outcomes was hypertension.It was then hypothesized that the increased mortality might be due to the subset of hypertension patients who were taking ARBs or ACEi as those may increase levels of ACE2 which has been shown in animals and possibly humans and ACE2 is the receptor for both SARS-CoV and SARS-COv2. So with more ACE2 would the results be a higher viral load?

On the other hand in an animal model of SARS-COV ARMS seems to reduce lung injury.

All this and a detailed recitation of the RAAS system as it relates to Corona viral infection can be found in the link found at the end of this post as can the citation for the BMJ article..That link is an article by Dr. GM Kuster et al published March 20 2020 in the European Heart Journal which reaches this conclusion:

In conclusion, based on currently available data and in view of the overwhelming evidence of mortality reduction in cardiovascular disease, ACE-I and ARB therapy should be maintained or initiated in patients with heart failure, hypertension, or myocardial infarction according to current guidelines as tolerated, irrespective of SARS-CoV2. Withdrawal of RAAS inhibition or preemptive switch to alternate drugs at this point seems not advisable, since it might even increase cardiovascular mortality in critically ill COVID-19 patients.

Thursday, March 19, 2020

A report from the chief epidemiologist from China's CDC in early March seemed to be reassuring.
Dr. Z.Wu speaking on an online conference on March 6 told the audience that transmission from presymptomatic people is rare and indicated that the rate was 1-5% among person in close contact with infected patients.

Subsequent reports and consideration of foci of rapid spread, (e.g. the Boston Biogen conference,the ill- fated cruise of the Diamond princess) suggest presymptomatic transmission may not be rare.

Japanese researchers found 634 of the 3711 passengers on the Diamond Princess tested positive and estimated 17.9 percemt were asymptomatic .

Using data from Tiajin China Dutch researchers used a mathematical model to estimate from Tiajin that the proportion of pre-symptomatic transmission was 62% ( 95% CI 50-76 %)

Note- these two analyses give estimates and not actual proven head counts of instances of spread from person without symptoms

Viral counts are higher in the nose and throat and peak earlier in covid 19 infections than was the case with SARS so that it seems very plausible that a pre-symptomatic person could transmit disease.

Further, even if the outer bounds of these estimates are still overestimates the likelihood of pre-symptomatic spread raises major questions regarding some of the current guidelines and advice from public health experts.

If exposed health care workers are allowed to return to work based on history of no symptoms and there is asymptomatic spread then other workers and patients are at risk.

Early on in the U.S, public health experts discouraged the use of masks by the general public at times with an apparently self contradicting argument that 1) masks don't really work and 2)masks should be reserved for doctors and nurses.

Of course, Surgical masks are not as effective a N-95 units but since viruses spread by droplets , masks offer some protection. Telling the public that masks don't work does not seem to be very good advice and that position seems to have largely walked back.

Early on US public health spokespeople downplayed possible pre-symptomatic transmission but now that has changed.In fact Dr. Scott Gottlieb said "We know there is asymptomatic spread".Further, in a 3/18/200 tweet he suggested that if the youth who are ignoring efforts to be socially distant they should be required to wear masks"

I believe also that high risk people who for good reason must venture into crowded areas ( e.g. groceries) should wear masks. I know I am- being at high risk by reason of age.

Friday, February 28, 2020

Although it was demonstrated at least as early as 1989 by CL Grines et al (1) that left bundle branch block (LBBB) could cause significant functional impairment of the left ventricule (LV), clinical description and general recognition of a LBBB cardiomyopathy as a clinical entity would require a decade or more.

Pacing the apex of the right ventricule was the default method for cardiac pacemaker implantation for many years and the path to recognition of a right venricular pacing induced cardiomyopathy and a better way to pace was neither short nor particularly straight.

In 2005 (Blanc et al ) and in 2013 (Vaillant) reports appears describing a dilated cardiomyopathy apparently induced by LBBB that in some instances were significantly reversed by cardiac resynchronization treatment (CRT).Blanc wrote "long standing LBBB may be a newly identified reversible cause of cardiomyopathy."

Further proof was offered by Barot et al (2017) in the form of a retrospective followup report.Thirteen of 94 LBBB patients with normal cardiac function (normal ejection fraction (EF) and no evidence of coronary artery disease developed a significant reduction in LV function over a variable time.

Not only is LBBB dyssynchronopathy heart failure now recognized it has become apparent that the usual heart failure meds do not seem very effective. In 2015, NC Wang et al reported the lack of response to medical therapy in 32 LBBB patients with new onset LBBB-associated idiopathic non-ischemic cardiomyopathy (NICM) and that "a high percentage were super-responders [to CRT]."

James Daubert and Edward Sze (3)argued in 2018 that the then current guidelines for implanting CRT require at least 3 months of guide-line directed therapy (GDMT) before implantation but there are no randomized clinical trials showing efficacy of medications and suggested that CRT should be considered for first line therapy rather than GDMT as many (most) symptomatic patients with LBBB do not respond to GDMT.

Since the early 1990s CRT has become an important treatment for heart failure with reduced ejection fraction (HFrEF) and delayed intra-ventricular conduction with the greatest benefit in those patients with LBBB.CRT traditionally has meant right ventricular pacing plus pacing the left ventricle from a vein on the surface of the left ventricle accessed through the coronary sinus.This is referred to as Bi-V. or biventricular pacing.More recently His Bundle pacing (HBP) has been suggested as being as good and perhaps better than Bi-V or at least as an alternative in cases in which the coronary sinus lead could not be placed.In cases in which the mechanical dyssynchrony is caused by an electrical problem an electrical "fix" seems necessary.HBP would seem to be the best fix being more physiological than Bi_V pacing .

Placing a pacing lead in the apex of the right ventricle was standard procedure for bradycardia indications for many years before EP cardiologists raised the question and then gathered evidence and finally concluded that in fact RV pacing could lead to significant loss of synchrony in the LV which resulted in heart failure in a significant number of patients

The similarities of the EKG in right apical pacing and LBBB certainly suggested possible functional impairment from RV pacing.Cardiologists were interested in some alterenative pacing method to avoid the harm that was becoming evident in RV pacing but no good alternative presented itself, at least not until HBP.Reports of septal pacing in place of apical pacing gave conflicting results.

As effective as traditional CRT (i.e. Bi-v) is some 30 % plus of patients with HF do not response while some seem to be "super-responders".Patients with narrow QRS complexes do not respond and those with a LBBB pattern are more likely to respond but all patients with a similar LBBB EKG pattern do not all respond to the same degree nor do they necessarily have the identical patern of LV electrical activation.All patients with an EKG designation of LBBB are not created equal.

The typical pattern of LV contraction described in LBBB is the following:

The interventricular septum moves quickly to the left in early systole (in the isovolumic contraction phase, i.e before aortic valve opens).The LV lateral wall is pushed outward and finally the electrical impulse traveling through myocytes reaches the lateral left wall area and it contracts pushing the septum to the right.

The initial left shift of the septum is mainly the result of the electrical impulse traveling from right to left (the opposite of the normal situation) and also from the pressure difference between the RV and LV as the RV contracts before the delayed LV contraction. This initial septal shift is called septal flash or septal beak and can be seen on M mode echo as well as on speckletracking echo.

Calle et al (2 ) have proposed that this septal flash may be the key to what "true LBBB" is- meaning the pattern of dyssynchrony that is responsible for the functional impairment and the pattern most "fixable" by CRT and by HBP as regards both LBBB and right apical pacing induced dysfunction.

Various other echo criteria have been proposed as the preferred measure to assess dyssynchrony and response to CRT without general agreement. About 50% of patients with the EKG pattern of LBBB are shown to have the septal flash and the associated dysfunctional out-of-sync LV contraction.

The septal flash indicates that the septum is activated from right to left initiating a sequence of dyssynchronous ventricular segmental contractions and relaxations that are deleterious to ventricular function and may result in remodeling and ultimately heart failure with reduced ejection fraction and is often reversible to varying degrees with CRT either by HBP or Bi-V.

So would CRT be expected to be useful in patients with RBBB since the septal activation is from left to right.In theory- no but Sharma ( 3) et al have reported significant clinical improvement

in some RBBB heart failure patients treated with HBP.Perhaps right to left septal activation ( as indicated by septal flash) is not a necessary condition for there to be improvement from CRT but I doubt one would see a super-response and the mechanism of benefit may relate more to improved atrial-ventricular synchrony improvement and not correction of an abnormal septal activation.